Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Aisling Barrett,John Quinn,Michelle Lavin,James O’Donnell,Philip Murphy,Siobhán Glavey,Patrick Thornton

doi:10.3390/jcm10163536

Aisling Barrett, John Quinn + Show 5 more

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https://doi.org/10.3390/jcm10163536

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Abstract

Multiple myeloma (MM) is associated with an increased risk of venous thrombosis (VTE). In the United Kingdom Medical Research Council (MRC) XI study of patients treated with immunomodulatory therapy, the VTE rate was 11.8% despite 87.7% of the patients being on thromboprophylaxis at the time of thrombosis. In order to effectively prevent VTE events in MM patients, a better understanding of patient and disease risk factors that might predict thrombosis is required. We performed a retrospective cohort analysis of over 300 newly diagnosed MM patients at a tertiary referral centre to determine the VTE rate, predictive factors for VTE, value of the Khorana score for MM VTE events and long-term mortality outcomes. Fifty-four percent of the patients were receiving thromboprophylaxis at the time of the VTE event. The mortality odds ratio was 3.3 (95% CI, 2.4–4.5) in patients who developed VTE in comparison to age-matched controls with MM. A younger age at diagnosis and higher white cell count (WCC) were found to be predictive of VTE events. Our data suggest that standard thromboprophylaxis may not be effective in preventing VTE events in myeloma patients, and alternative strategies, which could include higher-intensity thromboprophylaxis in young patients with a high WCC, are necessary.

Highlights

Multiple myeloma (MM) is a plasma cell malignancy that confers up to a 9-fold increased risk of venous thromboembolism (VTE) [1]
The patients at highest risk include those treated with immunomodulatory drugs (IMiDs) such as thalidomide or lenalidomide, for whom the VTE rate has been reported to be as high as 11.8% in the United Kingdom Medical Research Council (MRC)-XI trial [2]
Strategies for VTE prevention in MM patients have been adopted from the cancer literature and associated guidelines and are based on risk stratification with the use of low-molecular-weight heparin (LMWH) or aspirin according to risk factors

Summary

Introduction

Multiple myeloma (MM) is a plasma cell malignancy that confers up to a 9-fold increased risk of venous thromboembolism (VTE) [1]. The proposed risk factors for VTE development include patient-related factors such as a personal history of VTE, obesity, glucocorticoid use and comorbidities, and myeloma-related factors such as renal disease, hyperviscosity, immobilisation due to bone disease and treatment-related effects. That these protocols may not be effective in identifying atrisk MM patients or in preventing VTE events [5]. This provides evidence that MM patients are a distinct population of cancer patients with likely alternative mechanisms of VTE development and risk factors at play. VTE has been associated with inferior survival outcomes in myeloma patients, even in the novel therapy era, making a focus on predictive markers and the pathophysiologic mechanisms of thrombosis in these patients imperative [6]

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